Evidence for social anxiety and impaired social cognition in a mouse model of fragile X syndrome.

Abstract

This study assessed social behavior in a mouse model of Fragile X syndrome (FXS), the Fmr1 (tm1Cgr) or Fmr1 "knockout" (KO) mouse. Both the KO and wild-type (WT) mice preferred to be near a novel conspecific than to be alone. However, during the initial interaction with a novel conspecific, (1) a greater proportion of the KO mice exhibited high levels of grooming; and (2) the average duration of nose contact with the stimulus mouse was significantly shorter for the KO mice, both indicative of increased arousal and/or anxiety. Both groups exhibited a robust novelty preference when the novel animal was a "preferred" mouse. However, when the novel mouse was a "nonpreferred" animal, both groups showed a diminished novelty preference but this effect was more pronounced for the WT mice. This blunted negative reaction of the KO mice to a nonpreferred animal may indicate that they were less proficient than controls in distinguishing between positive and negative social interactions. These findings provide support for the use of this animal model to study the autistic features of FXS and autism spectrum disorders.

Deletion of Fmr1 results in sex‐specific changes in behavior

“…As such, a surprising finding of this study was that Fmr1 KOs show no change in investigation time in social tasks across both sexes. One other study reported similar social preference in the three‐chambered social task between Fmr1 WT and KO mice (McNaughton et al., 2008). These discrepancies may be as a result of a variety of environmental and methodological factors.…”

Modeling fragile X syndrome in the <i>Fmr1</i> knockout mouse

“…In the five-choice serial reaction time task, Fmr1 KO mice demonstrated heightened perseveration and responding during novel rule acquisition, which normalized with training (119). Fmr1 KO mice also exhibited higher levels of self-grooming, a repetitive behavior, than wildtype controls (89,133). Additionally, Fmr1 KO mice buried more marbles in the marble burying test (93,107,124), a measure of repetitive behavior (134).…”

Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach us

“…In addition, Fmr1 KO males display reduced social interaction with novel females (Mineur et al 2006) as well as impaired social dominance with unfamiliar mice (Spencer et al 2005). Such deficits may be explained by the enhanced anxiety aspect, as seen by increased rearing and digging behavior the Fmr1 KO mice exhibited in the presence of another mouse (McNaughton et al 2008;Mines et al 2010;Liu et al 2011). Impaired preference for unfamiliar mice may indicate lack of interest in novelty and/or impairment to discriminate between familiar and novel mice.…”